The specific aims of this research proposal are to identify stem cells in the chick embryo that can give rise to kidney tissue, and to characterize the mechanism by which this differentiation to kidney occurs, using both kidney and non-kidney derived stem cells. The initial analysis of what type of stem cells can give rise to kidney will be done with neural stem cells because there is existing evidence that neural stem cells can differentiate into both mesonephric mesenchyme and epithelium, a tissue that clearly becomes kidney in normal development. In the long-term, an understanding of this topic will have positive medical applications with respect to treating damaged kidneys or kidney disorders and will have advanced the current understanding of kidney development and stem cell differentiation. First quail neural stem cells, propagated as neurospheres, will be tested for their ability to differentiate into kidney tissue. A quail specific antibody will be use to track quail cell progenitors and study kidney differentiation. Stem cells from the metanephric kidney will be identified and isolated with a nucleotide analog (tritiated thymidine or bromodeoxyuridine). Stem cells divide slowly (retaining the nucleotide analog) in comparison to other cell populations and potential stem cells will be identified based on this characteristic. These stem cells, both kidney and non-kidney will be used to discover what tissues and molecules are required for kidney differentiation, utilizing intraembryonic implants and explant co-cultures.